In order to better understand the mechanisms by which the T cell repertoire is generated, the T cell response to Qa region MHC antigens was analyzed with respect to the recognition capabilities of the various functional T cell subpopulations. The results of these studies indicate that Qa specific CTL possess a typical class I specific repertoire in that they recognize self plus X and do not require intentional in vivo priming if adequate help is provided. In contrast, unlike the helper T cell response to most class I antigens, Qa specific Lyt2+ helper T cells could not be detected. It is concluded that although Qa-region antigens differ from other class I MHC antigens in that they have been reported to be 1) expressed on the cell surface in lower amounts, 2) are not extensively polymorphic, and 3) appear to be expressed predominantly on cells of the hematopoetic lineage, the Qa-specific CTL repertoire does not appear to be unique. The uniqueness of the Qa-specific helper cell repertoire remains to be determined.